Use of inotropic agents in advanced heart failure: pros and cons.

BACKGROUND: Use of inotropic agents in advanced heart failure (HF) has over time been evaluated in several randomized, controlled clinical trials (RCTs). However, the evidence for both efficacy and safety is conflicting. SUMMARY: In this narrative review, the evidence for and role of inotropes in advanced HF are outlined. Readers are provided with a comprehensive overview of key-findings from 23 important RCTs comparing orally or intravenously administered inotropes. Clinically relevant pros and cons of inotropic regimens are summarized to guide the clinician in the management of advanced HF patients in different settings (e.g., out-patient, in-patient, and intensive care unit). Finally, future perspectives and potential new agents are discussed. KEY MESSAGES: Long-term use of inotropes in advanced HF is controversial and should only be considered in selected patients (e.g., as palliative or bridging strategy). However, short-term use continues to play a large role in hospitalized patients with cardiogenic shock or severe decompensated acute HF.

Importance of heart failure duration for development of pulmonary hypertension in advanced heart failure.

BACKGROUND AND OBJECTIVES: Pulmonary vascular resistance (PVR) is critical when evaluating candidacy for advanced heart failure (HF) therapies, but risk factors for elevated PVR are not well studied. We hypothesized that HF duration would be associated with elevated PVR. METHODS: Danish single-center registry of consecutive in- and outpatients undergoing right heart catheterization as part of advanced HF work up. The relation between HF duration and PVR was estimated by regression analysis. Finally, the relation between PVR and long-term mortality was assessed by Cox proportional hazards regression and Kaplan-Meier analyses. RESULTS: A total of 549 patients (77% men, median age 54 (43-61) years, median HF duration 1.6 years (0.1-7.1)) were included. Univariate linear regression displayed an association between longer HF duration and increasing PVR (p = 0.014). PVR > 3 WU was present in 92 patients (17%) who were older (median p < 0.001) and had longer HF duration (p = 0.03). HF duration (per 1 year increase) did not predict PVR > 3 WU after adjustment for covariables (OR 1.00; p = 0.99). During a mean follow-up time of 4.5 years, there were 240 (44%) deaths. Increasing PVR was associated with elevated all-cause mortality risk (adjusted HR 1.24; p < 0.001). PVR > 3 WU was associated with higher mortality (adjusted HR 1.49; p = 0.027). CONCLUSION: Longer duration of HF was associated with higher PVR in patients with advanced HF, but this association disappeared in multivariate analyses. Longer HF duration per se likely does not cause elevated PVR and should not discourage evaluation for heart transplantation.

Diagnostic yield and long-term outcome of nonischemic sudden cardiac arrest survivors and their relatives: Results from a tertiary referral center.

BACKGROUND: Cardiac arrest may be the first manifestation of most inherited cardiac diseases. International guidelines recommend screening of relatives of sudden cardiac arrest (SCA) survivors if an inherited cardiac disorder is suspected. OBJECTIVE: The purpose of this study was to assess the prevalence and spectrum of inherited cardiac diseases and the long-term outcome in a consecutive cohort of nonischemic SCA survivors (probands) and their relatives. METHODS: This retrospective study consecutively included probands and their relatives referred to our tertiary center for family screening between 2005 and 2018. All participants underwent a systematic workup and follow-up protocol. Data were retrieved from medical records. RESULTS: We included 155 probands (age 41.2 ± 15.5 years; 61% male) and 282 relatives (age 35.7 ± 18.8 years; 51% male). Mean follow-up was 7.1 years for probands and 4.4 years for relatives. We identified an inherited cardiac disease in 76 (49%) probands and 42 (15%) relatives. An implantable cardioverter-defibrillator was inserted in 147 (95%) probands and 9 (3%) relatives. During follow-up, 4 (3%) probands and 3 (1%) relatives died, and 37 probands and 2 relatives received appropriate shock therapy. All relatives received genetic counseling, and 18 (6%) relatives started pharmacologic treatment during follow-up. CONCLUSION: Systematic workup of nonischemic SCA survivors and their relatives identified an inherited cardiac disease in 49% of referred probands and 15% of their relatives. The favorable long-term prognosis of diagnosed relatives probably not only reflects lower age but also the effects of early diagnosis, treatment, and follow-up. These findings support systematic workup of SCA survivors and their relatives.

Diagnostic findings and follow-up outcomes in relatives to young non-autopsied sudden death victims.

BACKGROUND: Guidelines recommend clinical assessment of relatives to young sudden cardiac death (SCD) victims in case the SCD was due to an inherited cardiac disorder. Work-up of relatives is guided by findings in the SCD victim. If post-mortem examinations have not been performed the work-up of relatives is challenged. METHOD: In this retrospective study we included families referred to our tertiary referral centre between 2005 and 2018 due to a possible SCD (pSCD) in the family. Autopsy had not been performed in any of the pSCD victims. The relatives underwent cardiac work-up focusing on putative presence of inherited cardiac disorders and genetic analysis in selected cases. A family diagnosis was only established if≥1 relative was diagnosed. The families were categorised as: 1) definite inherited cardiac diagnosis, 2) borderline diagnosis, or 3) undiagnosed. RESULTS: We assessed 149 relatives (43 ± 16 years, 48% men) from 84 pSCD non-autopsied cases (44 ± 11 years, 79% men). In 11 (13%) families a definite inherited cardiac diagnosis was established, a borderline diagnosis in 8 (10%) families, and 65 (77%) families remained undiagnosed. One third of the diagnosed relatives were offered pharmaco- or device-based therapy. During follow-up for 4.7 ± 3.6 years no relatives from the families with definite diagnoses died. No events were seen in the groups with borderline or no diagnoses. CONCLUSION: The diagnostic yield and need for treatment in diagnosed relatives warrant work-up, also of families with non-autopsied pSCD victims. No or reduced follow-up of relatives without signs or symptoms of heart diseases may be safe.

Diagnostic yield in victims of sudden cardiac death and their relatives.

AIMS: International guidelines recommend cardiogenetic screening in families with sudden cardiac death (SCD) if the suspected cause is an inherited cardiac disease. The aim was to assess the diagnostic yield of inherited cardiac diseases in consecutively referred SCD families. METHODS AND RESULTS: In this single-centre retrospective study, we consecutively included families referred to our tertiary unit between 2005 and 2018 for screening due to SCD. Following evaluation of premortem medical records and postmortem findings for the proband, the families underwent a guideline-based screening protocol. Relatives were followed and cardiovascular events registered. In total, 304 families with 695 relatives were included. In probands, mean age at death was 39 years (75% males) and in relatives mean age at screening was 35 years (47% males). The proband-diagnosis was established through autopsy findings (n = 89), genetic analyses (n = 7), or based on premortem findings (n = 21). In the remaining 187 families with borderline/no diagnosis in the proband, screening of relatives yielded a diagnosis in 26 additional families. In total, an inherited cardiac disease was identified in 143 out of 304 families (47%). In relatives, 73 (11%) were diagnosed. Arrhythmogenic right ventricular cardiomyopathy (n = 16) was the most common diagnosis. During follow-up (mean 5.5 years), a low rate of serious cardiac events was observed (no SCD events). CONCLUSION: Forty-seven percent of SCD families were diagnosed. Eleven percent of the screened relatives received a definite diagnosis and were offered treatment according to guidelines. A low rate of serious cardiovascular events was observed among SCD relatives.